Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis.
Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis.
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DOI：
10.1186/1465-9921-8-10
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发表时间：
2007-02-08
影响因子：
5.8
通讯作者：
Crystal, Ronald G.
中科院分区：
文献类型：
--
作者：
Gelbman, Brian D.;Heguy, Adriana;O'Connor, Timothy P.;Zabner, Joseph;Crystal, Ronald G.
香烟烟雾通过对上皮细胞的直接损伤破坏由气道上皮建立的保护屏障，导致细胞死亡。由于吸烟者的气道上皮的形态通常不显示坏死，因此响应于香烟烟雾的上皮细胞死亡的最可能机制是细胞凋亡。我们假设香烟烟雾直接上调凋亡基因的表达，这可能在气道上皮细胞凋亡中发挥作用。通过支气管镜检查对13名表型正常的吸烟者和9名非吸烟者的匹配队列获得的气道上皮细胞进行微阵列分析，以确定与凋亡相关的吸烟调节的特定基因。在上调的凋亡基因中有pirin（3.1倍，p < 0.002），一种铁结合核蛋白和转录辅因子。使用暴露于香烟烟雾提取物（CSE）和编码pirin cDNA的腺病毒载体（AdPirin）的人支气管细胞进行体外研究，以测试香烟烟雾对pirin表达的直接影响和pirin表达对细胞凋亡的影响。定量TaqMan RT-PCR证实吸烟者的气道上皮中的pirin表达与非吸烟者相比增加2倍（p < 0.02）。应用于原代人支气管上皮细胞培养物的CSE证明，吡林mRNA水平以时间和浓度依赖性方式增加（p < 0.03，所有条件与对照相比）。与对照腺病毒载体相比，使用载体AdPirin在人支气管上皮细胞中过表达pirin与通过TUNEL测定（5倍，p < 0.01）和针对细胞质核小体的ELISA（19.3倍，p < 0.01）评估的凋亡细胞数目的增加相关。这些观察结果表明，pirin的上调可能代表香烟烟雾诱导气道上皮细胞凋亡的一种机制，这一观察结果对香烟烟雾诱导的疾病的发病机制具有影响。
Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis. Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis. Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector. These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases.
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影响因子：
8
作者：
Duxbury, MS;Ito, H;Whang, EE
通讯作者：
Whang, EE
影响因子：
5.7
作者：
Heguy, A;Harvey, BG;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
2.9
作者：
KE, Y;REDDEL, RR;HARRIS, CC
通讯作者：
HARRIS, CC
DOI：
10.1164/ajrccm.160.supplement_1.11
发表时间：
1999-11-01
影响因子：
24.7
作者：
Mills, PR;Davies, RJ;Devalia, JL
通讯作者：
Devalia, JL
DOI：
10.1164/ajrccm.159.2.9804080
发表时间：
1999-02-01
影响因子：
24.7
作者：
Morrison, D;Rahman, I;MacNee, W
通讯作者：
MacNee, W